Alpha-smooth Muscle Actin-positive Cancer-associated Fibroblasts Secreting Osteopontin Promote Growth of Luminal Breast Cancer

Overview

Journal Cell Mol Biol Lett

Publisher Biomed Central

Specialties Biochemistry
Cell Biology
Molecular Biology

Date 2022 Jun 11

PMID 35690734

Authors

Anna Muchlinska

Anna Nagel

Marta Popeda

Jolanta Szade

Magdalena Niemira

Jacek Zielinski

Jaroslaw Skokowski

Natalia Bednarz-Knoll

Anna J Zaczek

Affiliations

Soon will be listed here.

Abstract

Background: Cancer-associated fibroblasts (CAFs) have been shown to support tumor development in a variety of cancers. Different markers were applied to classify CAFs in order to elucidate their impact on tumor progression. However, the exact mechanism by which CAFs enhance cancer development and metastasis is yet unknown.

Methods: Alpha-smooth muscle actin (α-SMA) was examined immunohistochemically in intratumoral CAFs of nonmetastatic breast cancers and correlated with clinicopathological data. Four CAF cell lines were isolated from patients with luminal breast cancer (lumBC) and classified according to the presence of α-SMA protein. Conditioned medium (CM) from CAF cultures was used to assess the influence of CAFs on lumBC cell lines: MCF7 and T47D cells using Matrigel 3D culture assay. To identify potential factors accounting for promotion of tumor growth by α-SMA CAFs, nCounter PanCancer Immune Profiling Panel (NanoString) was used.

Results: In luminal breast cancer, presence of intratumoral CAFs expressing high level of α-SMA (13% of lumBC group) correlated with poor prognosis (p = 0.019). In in vitro conditions, conditioned medium obtained from primary cultures of α-SMA-positive CAFs isolated from luminal tumors was observed to enhance growth of lumBC cell line colonies in 3D Matrigel, in contrast to CM derived from α-SMA-negative CAFs. Multigene expression analysis indicated that osteopontin (OPN) was overexpressed in α-SMA-positive CAFs in both clinical samples and in vitro models. OPN expression was associated with higher percentage of Ki67-positive cells in clinical material (p = 0.012), while OPN blocking in α-SMA-positive CAF-derived CM attenuated growth of lumBC cell line colonies in 3D Matrigel.

Conclusions: Our findings demonstrate that α-SMA-positive CAFs might enhance tumor growth via secretion of OPN.

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